Expertise in medicating depression requires experience with all types of antidepressants, including several medications within each type. Likewise, electroconvulsive therapy (ECT) proficiency includes experience with each of the modern electrode placements, of which there are four. Besides traditional bilateral and right unilateral placements, ECT electrode placement includes bifrontal and left anterior right temporal (LART) placements. In comparing antidepressant drugs, clinical trials have proven few differences of statistical significance, and useful proven differences are still more unusual. Analogously, few differences have been proven between ECT electrode placements, and many reported differences can be accounted for by large differences in electrical stimulus dosage. Still, the absence of proven differences does not show that there are no useful variations. This paper reviews the meaningful differences that are generally appreciated from clinical experience and biomedical principles for ECT electrode placement as well as antidepressant drugs.